Gastrointestinal pain is a symptom of many conditions, diseases and disorders associated with the gastrointestinal tract. Functional abdominal pain, refers to recurrent abdominal pain. The vast majority of patients with recurrent abdominal pain have “functional” or “non-organic” pain, meaning that the pain is not caused by physical abnormalities. Various motility disorders are also associated with pain and constipation or diarrhea. The term is used to describe a variety of disorders in which the gut has not developed properly or lost its ability to coordinate muscular activity due to various causes.
Such disorders may manifest in a variety of ways, and includes but are not limited to the following:
Abdominal distention
Recurrent obstruction
Abdominal colicky pain
Constipation
Gastroesophageal reflux disease
Intractable, recurrent vomiting
Diarrhea
Irritable bowel syndrome (IBS)
Inflammatory bowel disease
Fecal incontinence
Infantile colic
Frequent recurrent abdominal pain (FRAP)
Regurgitation
Food intolerance
In a broad sense, any significant alteration in the transit of foods and secretions into the digestive tract may be considered an intestinal motility disorder and this is type of disorder is often associated with gastrointestinal pain.
Proper coordinated movements of the stomach and intestines are required to digest and propel intestinal contents along the digestive tract. The patterns of contraction and relaxation necessary for proper motility of the gastrointestinal (GI) tract are complex and use the nerves and muscles within the GI walls. Every day, at any time, many factors can influence GI motility, e.g. physical exercise and emotional distress. Newborn infants have to develop the complex system of motility in the GI tract. Dysfunctional gastrointestinal motility is often associated with GI pain.
Aging, dementia, stroke, Parkinson disease, spinal cord injuries, rectal tears during birthing, diabetes, surgical complications and neuromuscular disorders, e.g. myasthenia gravis, may cause motility disorders that are associated with pain.
Irritable bowel syndrome (IBS), a commonly diagnosed disorder of intestinal motility and GI pain, has been considered a disease of the colon for decades, but research on GI motility has demonstrated that underlying motility disturbances can occur also in the small bowel. IBS can often be accompanied by GI pain and TRPV1 immunoreactivity has been shown to be markedly increased in IBS patients (Akbar, Yiangou et al, Gut 2008).
Constipation, often associated with GI pain, is the most common digestive complaint in the United States but despite its frequency, often remains unrecognized until the patient develops secondary disorders, such as anorectal disorders or diverticular disease. As mentioned previously, GI pain is a common symptom of constipation.
Constipation is quite common during pregnancy. The muscle contractions that normally move food through the intestines slow down because of higher levels of the hormone progesterone and possibly extra iron taken as prenatal vitamin. This is often also accompanied by lower abdominal pain.
Constipation is also associated with increased age and the so called “the aging gut” commonly found especially in people over 70 and in chronic care institutions.
At the other end of the aging spectrum intestinal motility disorders, persistent or excessive crying from infant colic is one of the most distressing problems of infancy. It is distressing for the infant, the parents, and the involved healthcare professionals. Colic pain often starts and stops abruptly
Intestinal hypermotility secondary to a presumed autonomic imbalance also has been proposed as one etiology for colic. Many of the mechanisms that regulate motor activity are immature in infants. The immaturity of these mechanisms may result in increased vulnerability to feeding intolerance. Thus, colic may be a common clinical manifestation in the subpopulation of infants who have maturational dysfunction in one or more of the aspects of motility regulation and often leading to GI pain for the infant.
Intestinal motility disorders applies to abnormal intestinal contractions often associated with GI pain, there are many different kinds of treatments and recommendations for the different disorders, some which work better than many others.
So there is an overall need and specific problems to solve for various motility disorders and pain disorders namely; How to best select agents to prevent or reduce gastrointestinal pain?
Transient receptor potential vanilloid 1 (TRPV1) is a Ca2+ permeant cation channel expressed in e.g. the peripheral nervous system (PNS), the central nervous system (CNS), the respiratory system and the gastrointestinal tract. TRPV1 is activated by physical and chemical stimuli, e.g. temperature, pH change and capsaicin, and is critical for the detection of nociceptive and thermal inflammatory pain. In the gastrointestinal tract, TRPV1 immunoreactivity can e.g. be found in visceral sensory afferents and TRPV1 cells transmit e.g. gastric pain sensation to the higher centers of the brain. TRPV1 is thought to be involved in several gastrointestinal conditions that are associated with pain sensations and TRPV1 immunoreactivity has been shown to be markedly increased in e.g. IBS (Akbar, Yiangou et al, Gut 2008). As an example of this, patients diagnosed with active inflammatory bowel disease demonstrate a greatly increased TRPV1 immunoreactivity in colonic nerve fibers (Wang, Miyares and Ahern, 2005 J. Physiol.).
Although TRPV1 is considered to be a potential target for developing drugs to treat different modalities of pain, the widespread expression of the receptor may result in adverse events limiting the use of systemic TRPV1 antagonists in treating gastrointestinal pain. In particular, antagonizing the receptor could potentially lead to cardiovascular complications as a result of decreased vasoactive peptide release.